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Browsing by Author "LaRue, Susan, committee member"

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    Analyzing early cancer etiology in golden retrievers using Golden Retriever Lifespan Study (GRLS) data
    (Colorado State University. Libraries, 2023) Hodo, Kiara, author; Magzamen, Sheryl, advisor; LaRue, Susan, committee member; Gutilla, Margaret, committee member
    Background: Although cancer is a burden in both humans and dogs, humans medicine is characterized by established health care organizations, interdisciplinary networks, and databases from which data and research can be complied and shared. No such organization exists in veterinary medicine. Individual registries provide useful data and information on cancer in dogs, but no mechanism exists to summarize data to detect cancer trends, breed-specific measurements of occurrence, and treatment responses. Therefore, there are vast knowledge gaps related to cancers in dogs, especially among early cases. The Golden Retriever Lifetime Study (GRLS) data collected by Morris Animal Foundation is a unique opportunity to evaluate cancer prevalence in a large number of golden retrievers with known pedigree. Data were evaluated for each state and compared to human cancer prevalence provided by the CDC. Differences in cancer prevalence between young and old dogs was evaluated, along with their resident state, sex status, and cancer type. Golden retrievers were recruited from 2012-2015 to participate in the GRLS cohort study and were confirmed to be free of life limiting conditions by a veterinarian. Owners had to have at least a 3-generation pedigree of their dog to be enrolled. Information regarding the dog's health and condition were recorded annually via owner and veterinarian questionnaire, as well as sample collections, and added to the GRLS study data. The GRLS data was refined and cleaned in SAS and R studio evaluate state of diagnosis, age at diagnosis, and sex at diagnosis. The highest prevalence of cancer among GRLS participants was in Louisiana (38.5%) with Arizona as the second highest (17.5%). A cluster of higher prevalence regions were observed in the upper east coast, similarly to the CDC's human data. Although the prevalence was highest in Louisiana and Arizona, neither were found to be statistically significant based on the difference of proportion calculations. A statistically significant difference was found in average age at diagnosis between male neutered and intact cancer dogs, but not when comparing female spayed and intact cancer bearing dogs or when comparing all 4 sex statuses. The average age at diagnosis based on tumor types (mammary, hemangiosarcoma, histiocytoma, lymphoma) was significantly different, most likely due to higher numbers of hemangiosarcoma cases in older dogs and histiocytoma cases observed in younger dogs. Older, male neutered dogs were more susceptible to hemangiosarcoma development (85.5% of cases were old), and younger dogs that had been spayed or neutered were more susceptible to histiocytomas (100% of cases were young). Discussion: One of the interesting findings of this analysis was that there was a statistically significant difference in average age at diagnosis between intact and neutered male dogs, but not between intact and spayed females. Small sample size of cancer dogs could have impacted the power of statistical test results and been a contributor to statistical insignificance seen throughout the analysis. Dogs moving multiple times throughout the duration of the study can affect interpretations and implications from prevalence by state findings. Prevalence was also calculated using only the total GRLS study population the resided in respective states as the denominator, effecting generalizability of the analysis findings.
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    Computational investigation of biological dose-volume outcome predictors in 29 canine nasal tumor patients treated with stereotactic radiation therapy
    (Colorado State University. Libraries, 2012) McBeth, Rafe, author; Zhang, Dongqing, advisor; LaRue, Susan, committee member; Custis, James, committee member; Ben-Hur, Asa, committee member
    The ability to mathematically model biological response to radiation dose in the tumors of cancer patients is a significant goal for the medical physics community. Although much work has been done in this area, novel treatment approaches are challenging the current knowledge of the radiation biology and oncology communities. In particular, doses five to ten times higher than traditional treatments are prescribed in stereotactic radiation therapy. These new treatment techniques are thought to have different mechanisms that cause cell death in comparison to classical treatments. These extraordinarily high doses are made possible by using advanced imaging, treatment planning, linear accelerator capabilities and immobilization to precisely target cancer while sparing healthy normal tissue. Biologically guided radiation therapy (BGRT) and biologically based treatment planning (BBTP) methods offer the next attractive step forward in radiation therapy. To examine the capabilities of biological based dose parameters, a mature data set of 29 canine nasal tumor patients was analyzed using the generalized equivalent uniform dose (gEUD) and the dose to a relative volume.Over one hundred individual predictors were inspected, with greater than five thousand individual tests, in search of optimal indicators of patient outcome.Testing showed that high negative gEUD values and the minimum dose to the tumor were highly significant predictors in the outcome of the patients. However, more robust techniqes need to be added to the analysis in order to validate these results.
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    Investigation of clinical gastrointestinal toxicity and underlying normal tissue damage associated with concurrent abdominal radiation therapy and tyrosine kinase inhibition
    (Colorado State University. Libraries, 2023) Prebble, Amber R., author; Boss, Mary-Keara, advisor; LaRue, Susan, committee member; Leary, Del, committee member; Thamm, Douglas, committee member
    Tyrosine kinase inhibitors (TKIs) may be combined with radiation therapy (RT) to enhance tumor control due to their anticancer and antiangiogenic effects; however, clinical evidence has emerged which suggests the treatment combination of RT and TKI may result in higher incidence of normal tissue side effects, dependent on the organs at risk in the radiation treatment field, than would be expected for either modality alone. We evaluated the incidence of gastrointestinal (GI) toxicity in canine cancer patients receiving concurrent hypofractionated abdominal RT and the TKI toceranib and compared to those receiving abdominal RT alone, toceranib alone, or concurrent non-abdominal RT and toceranib. Medical records of canine cancer patients were retrospectively reviewed and identified dogs were included in the following treatment categories: dogs which received RT to a portion of the abdomen and concurrent TOC (n = 19), abdominal RT alone (n = 29), TOC alone (n = 20), or non-abdominal RT plus TOC (n = 9). Toxicities were graded using the Veterinary Cooperative Oncology Group - Common Terminology Criteria for Adverse Events criteria and compared to published data on TOC-associated GI toxicity. Patients receiving TOC while undergoing abdominal RT had significantly increased rates of any grade of diarrhea (p = 0.002), hyporexia (p = 0.0045), and vomiting (p = 0.003), as well as severe hyporexia (p = 0.003) when compared across the treatment groups. This retrospective study revealed significantly increased incidences of GI toxicity when abdominal RT was combined with TOC in canine patients. Following these findings, we investigated the morbidity and underlying histological changes associated with combined abdominal RT and the TKI sunitinib in a mouse model. Prior to the experimental study, we identified a dose of abdominal RT in CD1 outbred mice which would induce mild GI toxicity according to weight loss and histologic changes in GI tissues harvested 7 days after irradiation; 12 gray (Gy) was selected as the optimal dose for the subsequent experiment. Twenty-five mice were then assigned to control (n = 5), sunitinib alone (n = 7), RT alone (n = 6), or RT + sunitinib (n = 7) groups and were weighed daily. All mice received daily oral gavage of vehicle or sunitinib (40 mg/kg) in vehicle for the entire study. On day 7 mice received 12 Gy abdominal RT or sham irradiation. On day 14 mice were euthanized and their entire GI tract was harvested for histopathologic evaluation, semiquantitative scoring of inflammation, and immunohistochemical quantification of cells positive for CD31 (vascularity) and Ki67 (proliferation). Major findings of this study included that mice in the combined therapy group, RT + sunitinib, lost significantly more weight than sunitinib alone (p < 0.0001) or RT alone (p = 0.0258). Mice in the RT alone group had a significant increase in GI vascular density, as determined by CD31, when compared to the SUN group (p = 0.0252). The mice in the RT + sunitinib group did not mount the same GI vascular response as the RT treated mice. The RT + sunitinib group had more crypt abscessation when compared to groups not receiving RT (vs. Control, p = 0.0076; vs. sunitinib alone, p = 0.0023). And, while it did not reach statistical significance when compared to the RT alone group, the RT + sunitinib group had more abscessation than RT alone (p = 0.0862) which could indicate a trend of higher levels of crypt abscessation with this combined treatment modality. The results from our canine retrospective clinical study and the preclinical mouse model experiment suggest that abdominal RT + TKI increases morbidity and GI toxicity at the RT and TKI doses investigated. Continued investigation of the underlying normal tissue effects associated with concurrent TKI and abdominal RT are recommended in order to determine whether combining these therapies could be optimized for safety and efficacy, such that GI toxicity is minimalized while achieving optimal tumor control.
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    Statistical methods for the detection and analysis of radioactive sources
    (Colorado State University. Libraries, 2014) Klumpp, John, author; Brandl, Alexander, advisor; Johnson, Thomas, committee member; Steinhauser, Georg, committee member; LaRue, Susan, committee member; Givens, Geof, committee member
    We consider four topics from areas of radioactive statistical analysis in the present study: Bayesian methods for the analysis of count rate data, analysis of energy data, a model for non-constant background count rate distributions, and a zero-inflated model of the sample count rate. The study begins with a review of Bayesian statistics and techniques for analyzing count rate data. Next, we consider a novel system for incorporating energy information into count rate measurements which searches for elevated count rates in multiple energy regions simultaneously. The system analyzes time-interval data in real time to sequentially update a probability distribution for the sample count rate. We then consider a "moving target" model of background radiation in which the instantaneous background count rate is a function of time, rather than being fixed. Unlike the sequential update system, this model assumes a large body of pre-existing data which can be analyzed retrospectively. Finally, we propose a novel Bayesian technique which allows for simultaneous source detection and count rate analysis. This technique is fully compatible with, but independent of, the sequential update system and moving target model.